It is known to the art that drugs such as alcohol, aminopyrine, antipyrine, methylurea, acetamide, sulfaguanidine, sulfadiazine, theophylline, and other low molecular weight nonelectrolytes are secreted through the skin or mucous membrane in sweat, saliva or the like. Other compounds which may be indicative of certain normal or disease conditions such as phenyalanine (phenylketonuria), sugar (diabetes), estriol (pregnancy), calcium (neoplasms) and copper (leukemia) for example, as well as normal and abnormal metabolites of other substances may be secreted in such fluids. Fluid collection is also used experimentally for determining biological requirements of various substances such as magnesium. If fluid samples are obtained and analyzed for these materials, the presence of such materials in the body can be detected. Such fluid collection therefore is useful in a wide variety of experimental, diagnostic, therapeutic and forensic medical purposes. While such fluids can be collected in numerous ways, a simple, easy to use technique utilizes an adhesive collection patch comprising a salt impregnated, fibrous, collecting pad which is mounted in an occlusive backing and adhered to the skin or mucous membrane of the mouth, vagina or other body cavity. The patch is removed after a predetermined time and analyzed for the presence of the chemical substance in question.
A typical patch is described in detail in Phillips, "An Improved Adhesive Patch for Long Term Collection of Sweat", Biomat., Med. Dev., Art. Org., 8(1), 13-21 (1980). While this patch yields, on an individual patch basis, a relatively constant uptake with time, there is a large variance in uptake, not only between individuals, but also between different patches on the same individual at the same site and between different patches on the same individual at different sites.
As can be seen from Baker, et al., "Measurement of Transepidermal Water Loss by Electrical Hygrometry", Arch. Derm., Vol. 96, pp. 441-452, Oct. 1967, water loss through the skin occurs through two independent processes, eccrine sweating and transepidermal diffusion. The volume of water loss through eccrine sweating is dependent upon many factors, such as ambient temperature, clothing, thermal stress, and level of exercise and can vary from a negligible amount to as much as 2 liters per hour under severe thermal stress. Transepidermal diffusion is a relatively steady passive process, the rate of which is dependent upon the ambient humidity, the skin surface temperature and the permeability of the skin to water loss. Water permeability of normal skin varies from site to site, from approximately 0.29 mg/hr.cm.sup.2 on the back to as much as 1.14 mg/hr.cm.sup.2 on the palm of the hand. In addition, variations in skin permeability are obtained as a result of any damage to the stratum corneum which is the major biological barrier to water loss in the skin. The damage can either be caused by injury, by intentional treatment with various materials such as hyperosmolar solutions, dimethyl sulfoxide, n-decylmethyl sulfoxide, dimethyl lauramide, ethanol, sodium lauryl sulphate or other materials known to have a permeation enhancing effect on the stratum corneum, or by stripping of the stratum corneum, such as occurs by the mere application and removal of an adhesive tape. The existing sweat collection patches, therefore, are capable of providing a qualitative indication of the presence or absence of a particular substance in the sweat during the collection period but are not capable of providing a quantitative indication of the average concentration of the agent during the sweat collection period. This is because they do not collect a constant volume of sweat per unit of time, independent of the aforementioned variables affecting the amount of sweat produced by the body in any particular time period at any particular body location and because they experience substantial back-diffusional losses.
According to our invention, however, we have devised a fluid collection patch in which the variation of collection rate between patches, between sites, and between individuals can be reduced or eliminated. Another advantage of the collection patches according to this invention is that the back-diffusion of fluid and therefore agent to be detected may be minimized, if not eliminated. By rendering the collection rate more uniform, constant and irreversible with time; quantitative analysis of the agent in the patch will yield a direct measurement of the average concentration of the agent in the fluid during the collection period.
For example, as Peck et al., have shown in the article, "Continuous Transepidermal Drug Collection: Basis for Use in Assessing Drug Intake and Pharmacokinetics." Journal of Pharm. and Biopharm. (9) 1, 1981, the amount of drug collected into a collection patch can be expressed by; ##EQU1## where K.sub.1c and K.sub.c1 the transfer process rates between the drug source A.sub.1 and the collection patch A.sub.c. The term K.sub.c1 A.sub.c represents the back diffusion rate from A.sub.c to A.sub.1. Collection patches accounting to our invention can eliminate this term so that the agent input rate into the collection patch is constant and reflects agent level in the fluid.
It is accordingly an object of this invention to provide an improved fluid collection patch.
It is another object of this invention to provide a fluid collection patch, the analysis of which will provide a time integrated average of the concentration of the agent in the fluid during the collection period.
It is another objection of this invention to provide an osmotically driven fluid collection patch with a semipermeable rate-controlling membrane.
It is another object of this invention to provide a fluid collection patch capable of collecting a constant volume of fluid per unit time during the collection period, independent of the volume of fluid produced per unit area of body surface.
It is another object of this invention to provide a collection patch capable of minimizing back diffusion of fluid and therefore agent to be detected.
It is another object of this invention to provide a fluid collection patch which protects the skin or mucous membrane from contact with hyperosmolar solutions.